This is a continuation of a Program Project Grant on basic and clinical studies related to osteoporosis. It includes an administrative core, molecular histology and transgenic animal core laboratories, and four major projects. The projects are 1) studies on the effects of sex hormones on bone formation and prostaglandin production, 2) studies on the role of glucocorticoids on collagen gene expression, 3) the development of new transgenic models to assess the hormonal and constitutive regulation of bone matrix synthesis in vivo and 4) studies on the effect of sex hormones on cytokine production and osteoclast formation and function. These projects will be closely integrated with other ongoing research efforts in bone metabolism currently being carried out at the University of Connecticut Health Center and its affiliated institutions, including laboratory studies and clinical research in the General Clinical Research Center (GCRC) and the Osteoporosis Center. The existence of a Program Project is osteoporosis has been vital in generating new research interactions among the many faculty involved in studies on bone and connective tissue metabolism and musculoskeletal disease at this institution. It has led to new initiatives in the application of molecular biology and genetic techniques to the pathogenesis of osteoporosis. Future interactions in the Program Project Grant should help us to provide new knowledge and lead to a better understanding of pathogenesis and more effective approaches to prediction, prevention and therapy in osteoporosis.